In most cases, the diagnosis of liver disease can be made using a carefully obtained history, physical examination and a few laboratory tests.

• Biochemical tests of liver function
  • Do not usually suggest a specific disease
  • Do suggest a category of liver disease (eg cholestatic versus hepatocellular patterns)
  • Can be normal in the presence of liver disease
  • Do not accurately assess the functionality of the liver
  • Best used in groups as a battery of tests to assess:
    • Hepatocellular damage
    • Cholestasis
    • Excretory function
    • Biosynthetic function
• Tests of hepatocellular damage
  • Laboratory testing
    • Aspartate aminotransferase (AST)
      • Found in numerous tissues including the liver, cardiac muscle, skeletal muscle, kidneys, brain and pancreas
    • Alanine aminotransferase (ALT)
      • Found primarily in the liver
  • Pathophysiology
    • Release of enzymes into the blood occurs when the liver cell membrane is damaged
      • Poor correlation exists between the degree of liver damage and the level of aminotransferases
      • Level of aminotransferases does not provide prognosis for liver necrosis or permanent damage
  • Elevated enzymes
    • Modest (<300 U/L - seen in any type of liver disorder)
      • Alcoholism
      • Gallstone-induced
      • Metabolic diseases
      • Acute and chronic hepatitis
    • Striking (>1000U/L)
      • Acute hepatitis
      • Toxin/Drug-induced hepatitis
      • Ischemic damage to the liver
• Tests of cholestasis
  • Laboratory testing
    • Alkaline phosphatase (ALP)
      • Isoenzymes include liver, bone, placental, and intestinal forms of ALP
      • Usually increased during periods of growth (eg, children, teenagers)
      • Elevated enzymes
        • Up to 3-fold elevation may be seen in any liver disease - not specific for cholestasis
        • Sole elevation of ALP should lead to isoenzyme testing or gammaglutamyl transferase and 5’ nucleotidase testing
        • Isolated elevation of the liver isoenzyme is suspicious for early cholestasis, but may also reflect tumor or granulomatous disease
        • Level of elevation is not helpful in distinguishing intrahepatic from extrahepatic causes of cholestasis
    • Gammaglutamyl transferase (GGT)
      • Very sensitive to small liver insults (e.g. alcohol consumption)
      • May be elevated in hepatocellular disease
    • 5’ nucleotidase (5’NT)
      • Very sensitive and specific for hepatobiliary disease
      • Can distinguish isolated elevations of ALP as liver related
    • Elevated ALT, AST, GGT and 5’NT
      • Highly suggestive of liver as source of disease
• Tests of excretory function
  • Laboratory testing
    • Serum bilirubin
      • 3 fractions - conjugated, unconjugated, and delta bilirubin (albumin-bound)
      • Elevated total bilirubin due to primarily
        • Unconjugated bilirubin - rarely reflects liver disease, commonly found in hemolytic disease
        • Conjugated bilirubin - almost always reflects hepatobiliary disease
        • Delta bilirubin - reflects hepatobiliary disease and remains elevated longer than other bilirubin fractions during the convalescent phase of liver disease
      • Causes jaundice when concentrations exceed 1.5 mg/dL
    • Urine bilirubin
      • Performed qualitatively using a urine dipstick
      • Any bilirubin found in the urine is the water-soluble conjugated fraction and its presence implies hepatobiliary disease
    • Blood ammonia
      • Liver converts ammonia to urea
        • Significant liver dysfunction results in elevated serum ammonia
      • Poor correlation between ammonia level and degree of liver disease
• Tests of biosynthetic function
  • Laboratory testing
    • Albumin - see Nutritional Assessment-Proteins (ARUP Consult topic)
    • Globulins
    • Coagulation factors
      • All factors except for factor VIII are produced in the liver
      • Factors II, V, VII and X are vitamin K sensitive (meaning they require adequate quantities of vitamin K for production)
      • Prothrombin time (PT) is a collective measure of factors II, V, VII and X
        • Elevated PT unresponsive to vitamin K supplementation suggests poor liver functionality

• Diagnosis
  • Initial screening for suspected liver disease should include AST, ALT, ALP and total bilirubin
    • Further testing based on results from initial screening battery
    • Prior to initiation of exhaustive evaluation of modestly elevated liver function tests (<2 times above normal for AST< ALT, ALP), recommend repeat serum testing